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哮喘儿童和健康儿童对鼻病毒 A 型和 C 型的 T 细胞反应。

T-cell responses against rhinovirus species A and C in asthmatic and healthy children.

机构信息

Telethon Kids Institute, The University of Western Australia, Perth, Australia.

School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.

出版信息

Immun Inflamm Dis. 2018 Mar;6(1):143-153. doi: 10.1002/iid3.206. Epub 2017 Nov 10.

Abstract

BACKGROUND

Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined.

OBJECTIVE

The aim of this study was to characterize and compare T-cell responses between RV-A and RV-C and to test the hypothesis that T-cell responses would differ between asthmatic children and healthy controls.

METHODS

A multi-parameter flow cytometry assay was used to characterize the in vitro recall T-cell response against RV-A and RV-C in PBMCs from children with acute asthma (n = 22) and controls (n = 26). The responses were induced by pools of peptides containing species-specific VP1 epitopes of RV-A and RV-C.

RESULTS

Regardless of children's clinical status, all children that responded to the in vitro stimulation (>90%) had a similar magnitude of CD4+ T-cell responses to RV-A and RV-C. However, asthmatic children had a significantly lower number of circulating regulatory T cells (Tregs), and healthy controls had significantly more Tregs induced by RV-A than RV-C.

CONCLUSIONS AND CLINICAL RELEVANCE

The comparable recall memory T-cell responses in asthmatic and control children to both RV-A and RV-C show that differences in the antibody and inflammatory responses previously described are likely to be due to regulation, with a demonstrated candidate being reduced regulatory T-cells. The reduced Treg numbers demonstrated here could explain the asthmatic's inability to appropriately control immunopathological responses to RV infections.

摘要

背景

鼻病毒(RV)A 型和 C 型感染是哮喘恶化的最常见原因,也是其他急性和慢性呼吸道疾病恶化的主要原因。这两种病毒在学龄前和学龄儿童中都很常见,尤其是对于 RV-C,它可能导致严重的症状和住院治疗的需要。虽然 RV 感染与哮喘之间的关联已得到充分证实,但 RV 感染影响哮喘恶化的适应性免疫机制仍有待确定。

目的

本研究旨在描述和比较 RV-A 和 RV-C 的 T 细胞反应,并检验 T 细胞反应在哮喘儿童和健康对照者之间存在差异的假设。

方法

使用多参数流式细胞术检测急性哮喘儿童(n=22)和健康对照者(n=26)PBMC 中针对 RV-A 和 RV-C 的体外回忆性 T 细胞反应。反应由含有 RV-A 和 RV-C 特异性 VP1 表位的肽池诱导。

结果

无论儿童的临床状况如何,所有对体外刺激有反应(>90%)的儿童对 RV-A 和 RV-C 的 CD4+T 细胞反应具有相似的幅度。然而,哮喘儿童的循环调节性 T 细胞(Tregs)数量显著降低,而健康对照者的 RV-A 诱导的 Tregs 数量明显多于 RV-C。

结论和临床相关性

哮喘和健康对照儿童对 RV-A 和 RV-C 均具有相似的回忆性记忆 T 细胞反应,表明先前描述的抗体和炎症反应的差异可能是由于调节所致,其中一个候选调节机制是 Treg 细胞数量减少。这里显示的 Treg 数量减少可以解释哮喘患者无法适当控制对 RV 感染的免疫病理反应的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce53/5818445/37211f73b9fa/IID3-6-143-g002.jpg

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